TY - JOUR
T1 - Valacyclovir pharmacokinetics and exploratory pharmacodynamics in young adults with epstein-barr virus infectious mononucleosis
AU - Vezina, Heather E.
AU - Balfour, Henry H.
AU - Weller, Dennis R.
AU - Anderson, Bruce J.
AU - Brundage, Richard C.
PY - 2010/7
Y1 - 2010/7
N2 - Primary Epstein-Barr virus (EBV) infection often results in infectious mononucleosis and is associated with serious sequelae. No treatment is approved for EBV infection, and an antiviral intervention would be significant. The objectives of this study are to characterize the pharmacokinetics and explore the pharmacodynamics of acyclovir in plasma and oral washings of 8 subjects receiving 7 days of valacyclovir 1500 mg twice daily for EBV infectious mononucleosis. Virologic and clinical responses are assessed over 12 days. Acyclovir is measured by liquid chromatography/ ultraviolet detection. EBV DNA is quantitated by TaqMan polymerase chain reaction. NONMEM VI and linear regression are used for data analysis. Acyclovir profiles in plasma and oral washings are consistent with a 1-compartment model. Final model estimates of clearance, volume of distribution, and fraction of acyclovir in oral wash supernatant are 49.9 L/h, 74.1 L, and 1.14%, respectively. The quantity of EBV DNA in oral washings and blood, and the severity of illness, measured by a graded scale, decrease during treatment. After treatment, viral rebound occurs in oral washings but not in blood, and the severity of illness continues to decline. Acyclovir pharmacokinetic parameters do not correlate with response metrics. These results support further studies of valacyclovir for EBV infectious mononucleosis.
AB - Primary Epstein-Barr virus (EBV) infection often results in infectious mononucleosis and is associated with serious sequelae. No treatment is approved for EBV infection, and an antiviral intervention would be significant. The objectives of this study are to characterize the pharmacokinetics and explore the pharmacodynamics of acyclovir in plasma and oral washings of 8 subjects receiving 7 days of valacyclovir 1500 mg twice daily for EBV infectious mononucleosis. Virologic and clinical responses are assessed over 12 days. Acyclovir is measured by liquid chromatography/ ultraviolet detection. EBV DNA is quantitated by TaqMan polymerase chain reaction. NONMEM VI and linear regression are used for data analysis. Acyclovir profiles in plasma and oral washings are consistent with a 1-compartment model. Final model estimates of clearance, volume of distribution, and fraction of acyclovir in oral wash supernatant are 49.9 L/h, 74.1 L, and 1.14%, respectively. The quantity of EBV DNA in oral washings and blood, and the severity of illness, measured by a graded scale, decrease during treatment. After treatment, viral rebound occurs in oral washings but not in blood, and the severity of illness continues to decline. Acyclovir pharmacokinetic parameters do not correlate with response metrics. These results support further studies of valacyclovir for EBV infectious mononucleosis.
KW - Epstein-Barr virus
KW - Infectious mononucleosis
KW - Pharmacodynamics
KW - Pharmacokinetics
KW - Valacyclovir
UR - http://www.scopus.com/inward/record.url?scp=77953784191&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77953784191&partnerID=8YFLogxK
U2 - 10.1177/0091270009351884
DO - 10.1177/0091270009351884
M3 - Article
C2 - 19897764
AN - SCOPUS:77953784191
SN - 0091-2700
VL - 50
SP - 734
EP - 742
JO - Journal of Clinical Pharmacology
JF - Journal of Clinical Pharmacology
IS - 7
ER -